Anaphylaxis is a rapid, potentially fatal, immediate hypersensitivity reaction characterized by laryngeal edema, bronchoconstriction, systemic hypotension and vascular leakage (1). Factors that predispose an individual to anaphylaxis include age, atopy, asthma, mastocytosis or activating mutations of mast cells (2, 3, 4). Pre-formed and newly formed biochemical mediators are released systemically during the degranulation of mast cells and basophils, including histamine, tryptase, carboxypeptidase A, prostaglandin D2, leukotrienes and platelet activating factor (5).
Platelet activating factor (PAF) is a pro-inflammatory phospholipid synthesized and secreted by various cell types such as mast cells, monocytes and fixed tissue macrophages (6). Circulating levels of PAF are, in part, controlled by the activity of the enzyme that degrades PAF, namely PAF-acetylhydrolase (PAF-AH) (7, 8). PAF has been implicated in a number of adverse pathological consequences due to disease or environmental triggers. Transduction of biological signals following the binding of PAF to its receptor on platelets, monocytes, macrophages and neutrophils, results in many of the manifestations of anaphylaxis (9). These effects of PAF are found in vivo and at normal PAF concentrations of 10−10 to 10−9 M, wherein PAF binds to specific G protein-coupled cell surface receptors (21).
Various research articles have been directed towards PAF and PAF-AH. For example, PAF receptor antagonists have been found to protect against anaphylaxis in mice, rabbits and rats (6). A synthetic PAF receptor antagonist is taught in U.S. Pat. No. 4,973,603. PAF-receptor knock-out mice were found to be protected from fatal anaphylaxis as compared to wild type mice with intact PAF receptors (10). The use of recombinant PAF-AH for blocking PAF-mediated pathological conditions is taught in U.S. Pat. No. 5,698,403 or 6,146,625 (the contents of both these patents are incorporated herein by reference). These references also teach an immunological method for detecting PAF-AH.
Although the aforementioned references teach prophylaxis and treatment for PAF induced inflammation, a need exists for a biomarker indicative of a predisposition to PAF induced anaphylaxis so that the risk of a severe or fatal anaphylactic episode can be determined ahead of time. In this regard, Vadas et al (19) found in a limited study that low levels of PAF-AH may be a biomarker for fatal peanut anaphylaxis. In the Vadas study, eight individuals who died of peanut-induced anaphylaxis were found to have low levels of PAF-AH activity. However, as concluded by Wang et al (22), there exists as yet no reliable test for diagnosing anaphylaxis.
Thus, a need exists for a biomarker for anaphylaxis. In particular, there exists a need to identify a biomarker for susceptibility or risk of anaphylaxis, and, more importantly, severe or fatal anaphylaxis resulting from various triggers.